Transplantation has emerged as the preferred method of treatment for many forms of end-stage organ failure. While short-term results have, improved long-term outcomes remain inadequate. The development of strategies to promote the acceptance of allogeneic tissues with greatly reduced or without the need for chronic immunosuppression would be of great benefit. To address this critical need, promising strategies need to be tested in a relevant pre-clinical model. The purpose of this study is to test a relevant strategy to meet this goal in the non-human primate pre-clinical model. Specifically this study will: (I) determine the effects of costimulation blockade (LEA29Y), basiliximab, sirolimus, and an intraportal infusion of donor splenocytes on allograft survival and the anti-donor immune response in the Rhesus macaque islet and renal transplant L models; and (2) to determine the effects of a chimeric anti-human CD45RB mAb alone or combined with sirolimus, an anti-ll.r2R mAb and an intraportal infusion of donor splenocytes on islet and renal allograft survival in Rhesus macaques. Success with one or more of these strategies will provide compelling evidence to test these relevant approaches in clinical trials.